Elucidating the neurochemical basis of LTP induction and maintenance in vivo

阐明体内 LTP 诱导和维持的神经化学基础

• 批准号: 10534841
• 负责人: Abhinav Goyal
• 金额: $ 4.7万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534841
• 关键词: Affect; Artificial Intelligence; Biological Process; Brain Injuries; Cell Nucleus; Cells; Conflict (Psychology); Corpus striatum structure; Data; Devices; Dopamine; Dopamine Antagonists; Dopamine-beta-monooxygenase; Electric Stimulation; Electrochemistry; Electrophysiology (science); Hippocampus (Brain); In Vitro; Individual; Intervention; Investigation; Long-Term Potentiation; Maintenance; Measures; Mediating; Mediator of activation protein; Memory; Methods; Microdialysis; Microelectrodes; Modeling; Molecular; Neurons; Neurosciences; Neurotransmitters; Norepinephrine; Oxidation-Reduction; Pharmacology; Phase; Physiological; Physiology; Play; Pulvinar structure; Rattus; Reaction; Resolution; Role; Sample Size; Sampling; Scanning; Signal Transduction; Techniques; Testing; Time; Tissues; Training; Validation; base; carbon fiber; experience; extracellular; in vivo; in vivo Model; inhibitor; insight; locus ceruleus structure; memory consolidation; memory encoding; neurochemistry; neuroregulation; noradrenergic; novel; oxidation; receptor; reuptake; signal processing; spatiotemporal

PROJECT SUMMARY Norepinephrine (NE)-containing neuronal cells in the locus coeruleus (LC) are thought to co-release dopamine (DA) from many of its projections, including into the hippocampus. Through DA and NE release, the LC is thought to play a major role in modulating hippocampal memory encoding through the maintenance of long-term potentiation (LTP), an integral mechanism for memory consolidation. Understanding the mechanisms by which the LC modulates memory is of fundamental importance to investigations into hippocampal memory circuitry and dynamics. However, because of their structural similarity, it has been difficult to ascertain the precise roles that DA and NE each have on LTP maintenance. In vivo microdialysis has been traditionally used in the past to measure tonic extracellular concentrations of molecules in the brain, but damage to tissue because of the size of the sampling probe and low spatiotemporal resolution make real-time tracking of tonic neurotransmitter concentrations, and their biological functions, problematic. Our lab has developed state- of-the-art voltammetric techniques capable of measuring tonic concentrations of neurotransmitters in real-time with very high spatial resolution. We hypothesize that by altering the voltammetric waveform applied in vivo and by developing a novel artificial intelligence based post-processing pipeline, very similar analytes such as DA and NE can be reliably resolved. Through accurate neurotransmitter identification and pharmacologic manipulation, we aim to ascertain the specific effects NE and DA have on hippocampal LTP. Additionally, we hypothesize that electrical stimulation of the LC will lead to increased hippocampal DA and NE release and enhanced LTP induction compared to no stimulation. The ability to resolve individual analytes based on their voltammetric signals has been an unsolved problem in electrochemistry and will enable tracking of their relative real-time contributions to LTP induction and maintenance in the hippocampus with high accuracy. A greater understanding of LTP induction and maintenance mechanisms is of vital importance to garnering an increased understanding of memory circuitry and physiology.

项目摘要 去甲肾上腺素（NE） - 基因座（LC）中含有神经元细胞（LC）被认为是从共同释放的多巴胺（DA） 它的许多预测，包括进入海马。通过DA和NE发布，LC被认为是专业的 通过长期增强（LTP）的维护来调节海马记忆的作用，这是一个积分 记忆合并的机制。了解LC调节内存的机制 对海马记忆电路和动力学的调查的基本意义。但是，由于他们的 结构上的相似性，很难确定每个NE在LTP维护中具有的确切作用。在 传统上，体内微透析被用于测量细胞外分子的分子中的分子 大脑，但由于采样探针的大小和低时空分辨率而对组织损害 跟踪补品神经递质浓度及其生物学功能，有问题。我们的实验室已经发展了国家 能够实时测量滋补神经递质浓度的伏安技术，并且非常 高空间分辨率。我们假设通过改变体内应用的伏安波形并开发一个 基于新颖的人工智能后处理管道，非常相似的分析（例如DA和NE）可以可靠 解决。通过准确的神经递质识别和药​​理操作，我们旨在确定特定 NE和DA对海马LTP的影响。此外，我们假设LC的电刺激将导致 与无刺激相比，海马DA和NE释放并增强了LTP诱导。能力 根据伏安信号解决单个分析物已是电化学中未解决的问题，并且将 可以跟踪其对LTP诱导和海马维护的相对实时贡献 准确性。对LTP归纳和维护机制有更深入的了解对于获得 对记忆电路和生理学的了解增加。